| First Author | Bhavsar SK | Year | 2012 |
| Journal | Biochem Biophys Res Commun | Volume | 425 |
| Issue | 1 | Pages | 6-12 |
| PubMed ID | 22814108 | Mgi Jnum | J:187168 |
| Mgi Id | MGI:5435629 | Doi | 10.1016/j.bbrc.2012.07.030 |
| Citation | Bhavsar SK, et al. (2012) AKT/SGK-sensitive phosphorylation of GSK3 in the regulation of L-selectin and perforin expression as well as activation induced cell death of T-lymphocytes. Biochem Biophys Res Commun 425(1):6-12 |
| abstractText | Survival and function of T-lymphocytes critically depends on phosphoinositide (PI) 3 kinase. PI3 kinase signaling includes the PKB/Akt and SGK dependent phosphorylation and thus inhibition of glycogen synthase kinase GSK3alpha,beta. Lithium, a known unspecific GSK3 inhibitor protects against experimental autoimmune encephalomyelitis. The present study explored, whether Akt/SGK-dependent regulation of GSK3 activity is a determinant of T cell survival and function. Experiments were performed in mutant mice in which Akt/SGK-dependent GSK3alpha,beta inhibition was disrupted by replacement of the serine residue in the respective SGK/Akt-phosphorylation consensus sequence by alanine (gsk3(KI)). T cells from gsk3(KI) mice were compared to T cells from corresponding wild type mice (gsk3(WT)). As a result, in gsk3(KI) CD4(+) cells surface CD62L (L-selectin) was significantly less abundant than in gsk3(WT) CD4(+) cells. Upon activation in vitro T cells from gsk3(KI) mice reacted with enhanced perforin production and reduced activation induced cell death. Cytokine production was rather reduced in gsk3(KI) T cells, suggesting that GSK3 induces effector function in CD8(+) T cells. In conclusion, PKB/Akt and SGK sensitive phosphorylation of GSK3alpha,beta is a potent regulator of perforin expression and activation induced cell death in T lymphocytes. |
